Most studies regarding plasma biomedicine applications mainly focus on the oxidative and/or nitrative stress on bacteria, cancer cells, and other treatment objects. In this study, we evaluate the protective effect of appropriate atmospheric pressure plasma jet (APPJ) treatments on oxygen and glucose deprivation (OGD)‐induced neural cell apoptosis, which is a major pathological process during ischemic stroke, based on the physiological functions of NO. Results show that APPJ treatment reduces the OGD‐induced apoptosis by weakening typical OGD injury consequences including loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytoplasm, lower antiapoptotic Bcl‐2 expression, and upregulating the proapoptotic protein Bax. Furthermore, APPJ increased intracellular NO production, which is closely related to the cytoprotective effect of APPJ.